Rhodium-catalyzed regioselective C-H functionalization via decarbonylation of acid chlorides and C-H bond activation under phosphine-free conditions

Article abstract of DOI:10.1021/ja803154h

Efficient rhodium(I)-catalyzed regioselective functionalization of aromatic C-H bonds has been realized with acid chlorides as the coupling partners via decarbonylation and C-H activation under phosphine-free conditions. Copyright

Full text of DOI:10.1021/ja803154h

Published on Web 06/10/2008
Rhodium-Catalyzed Regioselective C-H Functionalization via
Decarbonylation of Acid Chlorides and C-H Bond Activation under
Phosphine-Free Conditions
Xiaodan Zhao† and Zhengkun Yu*,†,‡
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning
116023, P. R. China, and State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. China
Received April 29, 2008; E-mail: zkyu@dicp.ac.cn
Table 1. Screening of Reaction Conditionsa
Transition metal catalyzed activation of aromatic C-H bonds
followed by new C-C bond formation is of considerable attraction in
organic synthesis because of no requirement for prefunctionalization
of the arene or heteroaromatic substrates by metalation or halogena-
tion.1 o-Arylation, alkenylation, or alkylation of sp2 C-H bonds
involving subsequent regioselective formation of C-C bonds assisted
cat.
mol %
temp time conversion
(°C) (h)
(%)b
by various functional groups under palladium, ruthenium, or rhodium
catalysis have received much attention.1,2 Arenes and heterocycles
usually undergo chelation-assisted C-H functionalization with organic
or organometallic coupling partners such as Ar-X (X ) I, Br, Cl,
OTs, OTf),3 organotin,4a organoboron,4b–e and arylzinc,4f reagents,
arylsilanes,5 alkenyl acetates,6 Ar2IBF4,7 haloolefins,8 olefins,9
alkynes,10 or some unactivated aromatic rings,11 producing the cross-
coupling products. Peroxides and diethyl azodicarboxylate have also
been used as the coupling partners for this purpose.12 Although a
variety of coupling partner compounds have been successfully
explored, the need to develop readily available coupling partners as
well as the corresponding effective catalyst systems is still strongly
desired in this area. Acid chlorides are usually cheap and readily
derived from their mother acids. Aroyl chlorides can be decarbonylated
to undergo Heck-type reactions or decarbonylative addition to alkynes
by means of palladium or rhodium catalysts.13,14 Herein, we report
the first protocol for regioselective functionalization of aromatic C-H
bonds using acid chlorides as the coupling partners via C-H bond
activation by rhodium(I) catalysis under phosphine-free conditions.
Palladium-catalyzed ligand-directed aromatic C-H activation to
form C-C bonds has been well documented.1 Subsequently, we
initially tested the coupling reaction of benzo[h]quinoline (1a) and
benzoyl chloride (2a) with a base in refluxing toluene using palladium
acetate as the catalyst. However, the arylation aimed at forming the
coupling product 3a via decarbonylation of 2a and C-H bond
activation did not occur even if an oxidant such as benzoquinone was
added to the reaction system. Using 3 mol % rhodium(I) complex
[Rh(COD)Cl]2 as the catalyst, the expected arylation did not take place
either (Table 1, entries 1-2). When 4 A molecular sieves were added
to the reaction mixture, the coupling was remarkably improved to form
the desired decarbonylative coupling product 3a (entry 3). The CO-
retentive coupling product, that is, 10-benzoyl benzoquinoline, was
not observed in the reaction. After the reaction conditions were
screened and optimized, the decarbonylative coupling product 3a was
afforded in 94% isolated yield using 5 mol% [Rh(COD)Cl]2 as the
catalyst, Na2CO3 as the base, and 4 A MS as the additive in refluxing
xylene at 145 °C for 16 h (entry 7). With KF or K3PO4 as the base,
1a was also efficiently transformed to the desired product (entries 8-9),
while an organic base such as EtiPr2N did not promote the reaction so
much. Carbonyl rhodium(I) complex [Rh(CO)2Cl]2 was also efficient
for the coupling (entry 10), while the ionic rhodium(I) salt
entry solvent
additive
base
Na2CO3 110 24
K2CO3
1
2
3
4
5
6
7
8
toluene [Rh(COD)Cl]2/3
toluene [Rh(COD)Cl]2/3
toluene [Rh(COD)Cl]2/3 4A MS K2CO3
xylene [Rh(COD)Cl]2/3 4A MS K2CO3
xylene [Rh(COD)Cl]2/3 4A MS Na2CO3 135 24
xylene [Rh(COD)Cl]2/5 4A MS Na2CO3 135 16
xylene [Rh(COD)Cl]2/5 4A MS Na2CO3 145 16
xylene [Rh(COD)Cl]2/5 4A MS KF
xylene [Rh(COD)Cl]2/5 4A MS K3PO4
xylene [Rh(COD)Cl]2/5 4A MS K2CO3
-
-
110 24
110 24
135 24
45
76
81
92
>99(94)
98
c
145 16
9
145 16 >99
145 16 93
10
11
12
13
14
xylene [Rh(CO)2Cl]2/5 4A MS Na2CO3 145 16 >99
xylene Rh(COD)2BF4/5 4A MS Na2CO3 145 16
xylene RhCl(PPh3)3/5 4A MS Na2CO3 145 16
xylene [Rh(COD)Cl]2/5 4A MS Na2CO3 145 16
27
15
15
d
a Reaction conditions: 1a, 0.3 mmol; 2a, 1.5 equiv; base, 2 equiv;
solvent, 3 mL. b Conversion of 1a determined by GC analysis. c Isolated
yield of 3a in parenthesis. d PPh3 (20 mol %) was added.
Table 2. C-H Functionalization of 1a via Decarbonylation and
C-H Bond Activationa
entry
R
2
product
yield (%)b
1
2
3
4
5
6
7
8
9
10
Ph
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
93
86
90
95
87
71
68
74
37
94
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
3-NO2C6H4
1-naphthalyl
C6H5CH)CH
PhCH2
2g
2h
2i
3g
c
3h (E/Z ) 23/1)
3i
3a
d
2j
s
a Reaction conditions: 1a, 0.5 mmol; 2, 1.5 equiv; [Rh(COD)Cl]2, 5
mol %; Na2CO3, 2 equiv; 4A MS; xylene, 3 mL; 145 °C, 16 h.
b Isolated yields. c Ratio determined by H NMR. d 2j, PhCOCOCl.
1
Rh(COD)2BF4 and Wilkinson’s catalyst only showed poor catalytic
activity (entries 11-13). In contrast to the reported Rh(I)/phosphine-
catalyzed C-H activation,4a,e,9 a phosphine ligand, for example, PPh3,
present in the reaction system dramatically retarded the coupling
reaction (entry 14).
Under the optimized conditions, reaction of 1a (0.5 mmol) with 2a
afforded the functionalization product 3a in 93% isolated yield (Table
2, entry 1). Other aroyl chlorides also efficiently underwent the coupling
reactions with 1a to form the desired products (3a-h) (entries 2-7).
† Dalian Institute of Chemical Physics.
‡ Shanghai Institute of Organic Chemistry.
9
8136 J. AM. CHEM. SOC. 2008, 130, 8136–8137
10.1021/ja803154h CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 3. C-H Functionalization of 1 via Decarbonylation of 2a or
2c and C-H Bond Activationa
Scheme 1. Proposed Mechanism
C-H activation via intramolecular ortho-chelating assistance in the
presence of a base. The desired product 3 is then produced by reductive
elimination of 6. Such a proton abstraction mechanism is plausible to
explain functionalization of the aromatic C-H bonds by acid
chlorides.3e,15
In summary, efficient regioselective functionalization of aromatic
C-H bonds has been realized by Rh(I) catalysis using acid chlorides
as the coupling partners via decarbonylative C-H activation with arene
or N-heteroaromatic substrates under phosphine-free conditions.
Exploration of the substrate scope and reaction mechanism will be
further investigated.
Acknowledgment. We are grateful to the National Natural Science
Foundation of China (Grant Nos. 20501018, 20772124) for financial
support of this research.
a Reaction conditions: 1, 0.5 mmol; 4A MS; xylene, 3 mL; 145 °C,
16 h. (A) [Rh(COD)Cl]2, 10 mol %; Na2CO3, 3 equiv; 2a or 2c, 4.0
equiv. (B) [Rh(COD)Cl]2, 5 mol%; Na2CO3, 2 equiv; 2a, 1.5 equiv.
b isolated yields. c R
e [Rh(COD)Cl]2, 10 mol %.
)
Ph (2a). d R
)
4-MeOC6H4 (2c).
Supporting Information Available: Experimental procedures, ana-
lytical data, and copies of NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
Styryl-functionalized product 3h was obtained in 74% yield through
the decarbonylation of trans-cinnamoyl chloride 2h and C-H bond
activation (entry 8). It is worth noting that arene 1a was decarbony-
latively benzylated by phenylacetyl chloride 2i in 37% yield (entry
9). Interestingly, acid chloride PhCOCOCl (2j) was efficiently coupled
with 1a, producing 3a in 94% yield through double carbonyl
elimination (entry 10).
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J. AM. CHEM. SOC. VOL. 130, NO. 26, 2008 8137